Polycyclic diketopyrimidines



rmul III Patented July I, 1947 UNITED STATES PATENT oFrlcE PoLYoYcLIo Allred W. Anish, Vestal, N. 9-K, to nine.

eral Aniline & Film CorpnratinnpNew York, N. Y., a corporation of Delaware i g No Drawing.

This invention relates to newpolycyclic diketopyrimidines and to a method for their production. More particularly, the invention relates to compounds which may be represented by the following general formula;

40 s c 1 z J; R

--N =(M),.-N

wherein M represents a methenyl group, Z represents the non-metallic atoms necessary to complete a heterocyclic nucleus, 11 is a positive odd integer not greater than 5, R represents an aryl group selected from the benzene and naphthalene series and Rrepresehts a hydrogen or acyl group.

"Ih ese compound-s readily react with heterd,

cyclic compounds usual cyanine dyes to new merocyanin-edyes, and are, tnerer-ore, highnucleus such as cf the thiazoli-neor SE-IGI-IaZOIiIIe series, e. g. thiazoline or selenazoline; or of the thiazole series; e.- g he'iiahydrobenzthiazole; or of the pyrazolone series, e. :g. fimhenylpyrazolone; or of the pyridine or quinolineseries, e; g. pyridine or quinoline, or :of the thia'zine series, such as thiazine.

The compounds of structure I may be prepared by reacting a compound having the following structure:

wherein has the same significance as indicated aboveywith a compound having the renewing Applicationbec'cmber :7, 1945, Serial No. 633,538

16 Claims. (01.260-s-1e2609f;

wherein represntsa methenyrmnp, a. is; 1 integer greater :5 andeR present groups such jas'menyl,

mph nyierrm I I Mdrepartieularlymmipohnum may be V KI) A diaryliormamidine when it is ifliSii'flditD ob t n acotmiound "of structure I where rn is li ar yiammcacroiein anil; when it is 166 btai h a commimd' DI strufiwi'al where siredtew nisB (3) yl aminmhah pentadicnhi amlwlmn it is he's eatc obtaiha compouhdhf ,stcuctube rwnere '5, x I I w communes (2) and (3 h rle rireierably in the form of their salts, such, for instance, as their hydrochlorides. are employed the reaction is carried out in the presence of strong bases such as triethylamine, piperidine, diethylamine, N-methylpiperidine and triethanolamine. Otherbases may also be employed as, for example, pyridine. The reactions can also be carried out in the presence of organic acid anhydrides, as for example, acetic, propionic and benzoic acid anhydri des. r

When compounds 10f Formulas II and III are reacted, compounds of Formula I are obtained in which R is hydrogen. The acylated derivatives of I are "obtained, that is, compounds in which R is acyl, by carrying out the reaction in the presence of an organic acid anhydride, such as acetic, propionic butyric or benzoic anhydrides. If desired, the reaction products of II and III may be first formed and then acylated to form the acylated derivatives.

In general, compounds II and III are utilized in equimolecularamounts, although a slight excess of either may be employed. Room temperatures may be employed. Heating facilitates the reaction. The reaction may be readily carried out at reflux temperatures. -If desired, the reaction may be carried out in the presence of diluents, as for example, alcohol, kerosene or the bases or acylating agents may themselves serve 1 as diluents.

Examples of compoimds bi Formula III and their salts are: diphenylformamidine, dinaphthylformamidine, dixylylformamidine, B-anilinoacrolein anil and its hydrochloride, fi-anilino-achloroacrolein anil and its hydrochloride, ,8- anilino-a-bromo-acrolein anil and their hydrochlorides, and glutaconic-aldehyde dianilide hydrochloride.

The polycyclic compounds of the type illustrated by Formula II above, from which the compounds of this invention are produced, may

be prepared from a large variety of starting materials. Any heterocyclic compound substituted by a primary amine group which readily undergoes the following tautomeric imino form will yield the corresponding bicyclic compound Z has the same significance as above. 7

In practice, the starting compounds illustrated by Formula II can be obtained by condensing the aforementioned amino-substituted heterocyclic compounds with ethyl malonate according to the procedure of Masters 8 Bogert, Journal of American Chemical Society, vol. 64- (1942), page 2709 or by the method described in Berichte vol. 57 (1924), page 1170. w More particularly, the process involved in preparing the intermediates of structure II comprises condensing amino-substituted heterocyclic compounds with ethyl malonate in the presence of alcoholic sodium ethylate. As examples of amino-substituted heterocyclic compounds which may be so converted into polycyclic compounds having the structure II, there may be mentioned 2-aminothiazoline, 2-aminose1enazoline, 2-aminodihydrothiazine, .2-amino-5-methylthiazoline, 2-amino-4-phenylthiazoline, Z-aminohexahydrobenzthiazole, 3-phenyl-5-aminopyrazolone and 2- aniinopyridine. When these compounds are condensed with ethyl malonate in the manner described, they result in compounds whichmay be represented by the following structural formulas:

From z-aminothiazoline mo (IJ/ o=o Ht-N 6H2 II o From Z-aminodihydrothlazine H: N 21H:

From 2 -amino-4-phenylthiazoline 4 From 2-aminohexahydrobenzthlazole fi H10 311 3 0:0 U) 5 Hz CHN (EH2 ll 0 From 3-phenyl-5-amlnopyrazolone /N o=o-c c=o J l I (0) CaHs- N CH:

From 2-aminopyridine t ii \N/ (M O=(\}\ /C=O 1,

The following examples will illustrate the mode of producing the compounds of Formula I Where n is one. Example 1 1120 1 0:0 H2 ---N =CHN4CaH5 (i OCH: 0

3.4 grams of compound (a) above, 3.9 grams of diphenyl formamidine and 30 cc. of acetic anhydride are refluxed for about one hour. A com- 0 pound of the above formula separates from the reaction mixture and can be recrystallized from methylalcohol.

' 7 Example 2 1.8 grams of compound (0) and 2 grams of diphenyl formamidine are reacted as in Example 1. A compound having the above formula is obtained.

4.4 grams of compound (1) and 3.9 grams of dlphenyl formamidine are reacted as in Example 1. A compound having the above formula is obtained.

By omitting, in the above examples, the acetic anhydride the corresponding anilinomethylene compounds are obtained in place of the acetanilidomethylene compounds. In such a. case it is advantageous to carry out the reaction in the presence of a diluent as for example, kerosene.

In the same manner as that illustrated by the above examples, other compounds of structure 11 may be reacted with diarylformamides to produce 5. the anilinomethlylene I and acylanilldomethylene derivatives. Thus, for example, compoflnds (b), (d), (e), (g) and (h) may 'betreated in the same manner as illustrated by the above examples.

The following examples will illustrate the mode of producing the compounds ofFormula I where n is 3.

Example 4 11,0 c=o In c'=cH-cH=oH-N-o.m

C OCHa I;

3.4 gramsof compound (a)-, 5.2 grams of ,6- anilinoacrolein anil hydrochloride and 25 cc. of acetic anhydride are heated under reflux for about 1 hour. A compound of theabove formula separates from the reaction mixture and can be recrystallized from methyl alcohol.

3.4 grams of compound (a) are allowed to react with 7 grams ofp-anilino-a-bromo-acrolein anil hydrobromide in the presence of 30 cc. of acetic anhydride as in Example 4. A compound of the above formula is obtained.

Example 6 H50 0 o=o at 1 =GHCH='CHN-CcHa cfiz \C/ 0011:;

Equlmolecular proportions of compound (c) and p-anilino-acrolein anil. hydrochloride are treated as in Example 4. A compound of the above formula is obtained.

2.4 grams of compound (9) 2.6 grams of 's-anilino-acrolein anil hydrochloride and 20 cc. of acetic anhydric are heated. under reflux for about an hour. A compound of the above formula separates and can be recrystallized from methyl aldride the corresponding -anilinoall'ylldene comallylidene compounds.

6 pounds" are-obtainedinstead or the 'y-acetanilidc- In such a case, reaction is preferably carried out in the presence or a strong organic base suchas, for example, piperidlne or triethylamine, preferably in an equimolecular amount, and a suitable diluent such as, for example, ethyl, n-propyl 0r isopropyl alcohol.

I'he 'y-anilinoallylidene compound can then be converted to the corresponding Y-acylanilidoallylidene compound by acylating it with a suitable acylating agent such as acetic anhydride.

In the same manner as illustrated in Examples 4-8, other compounds of Formula II may be reacted with a ylaminoacrolein anil and their salts to produce the Y-anilinoallylidene and 'yacylanilidoallylidene compounds. Thus, for examples, compounds (b), (d), (e) and (h) may be treated in the same manner as illustratedby Examples 4-8.

The following examples will illustrate the mode of producing the compounds for Formula I where n is 5.

3.4 grams of compound (a), 516 grams of glutaconic aldehyde dianilide hydrochloride and 30 cc. of acetic anhydride are heated under reflux for about 1 hour. A compound of the above formula separates from the reaction mixture and can be recrystallized from methyl alcohol.

C a COOHa 2.2 grams of compound (I) and 2.8 of glutaconic aldehyde dianilide hydrochloride are reacted as in Example 9. A compound having the above formula is obtained.

By omitting in Examples 9 and 10 the acetic anhydride the corresponding w-anilino-A2A- pentadienylidene compounds are obtained instead of the w-acetanilido-A2,4-pentadienylidene compounds. In such a case the reaction is preferably carried out in the presence of a strong organic base such as, for example, piperidine or triathylamine, in preferably an equimolecular amount and a suitable diluent such as, for example, ethyl, n-p'ropyl or iso-propyl alcohol. Thus, for example, by omitting the acetic anhydride in Example 9, and substituting therefor cc. of isopropyl alcohol and? grains of triethylamine and refluxing for 20 minutes, one obtains acompound of the following formula:

To produce the compound of Example 9, this is acylated by boiling with cc. of acetic anhydride.

In the same manner as illustrated in Examples 9 and 10, other compounds of Formula II may be reacted with w-ary1amino-A2A-pentadienal smile and their salts to produce the a-anil ino-A ZA-pentadienylidene and w-aeylanihdo-MA- pentadienylidene compounds. Thus, for example,

compounds (22), (c), (d), (e), (g) and (hymay be treated in the same manner as illustrated by 7 Examples 9 and 10.

In each of the above examples, the acetic an hydride maybe substituted by propionic or benzoic anhydride as well as other anhydrides.

l. Polycyclic diketopyrimidines characterized by the following formula:

wherein M represents a methenyl group, Z represents the nonmetallic atoms necessary to complete a heterocyclic nucleus, n is a positive odd integer not greater than 5, R is an aryl group selected from the class consisting of the benzene and naphthalene series, and R, is a substituent selected from the group consisting of hydrogen and acyl groups.

2. Polycyclic diketopyrimidines characterized by the following formula:

wherein Z represents the non-metallic atoms necessary to complete a heterocyclic nucleous, R is an aryl group selected from the class consisting of the benzene and naphthalene series, and. R is a substituent selected from the group consisting of hydrogen and acyl groups.

3. Polycyclic diketopyrimidines characterized by the following formula:

wherein Z represents the non-metallic atoms necessary to complete a heterocyclic nucleus, R is an aryl group selected from the class consisting of the benzene and naphthalene series, and R is a substituent selected from the group consisting of hydrogen and acyl groups.

4. Polycyclic diketopyrimidines characterized by the following formula:

I ,.0 o=o z I R "-N =CH-CH=OHOH=OHN where Z represents the non-metallic atoms necessary to complete a heterocyclic nucleus, R is an aryl group selected from the class consisting of the benzene and naphthalene series, and R is a substituent selected from the group consisting of hydrogen and acyl groups.

8 5, Polycyclic diketopyrimidines characterized by the following formula:

wherein M represents a methenyl group, Z represents the non-metallic atoms necessary to complete a thiazole nucleus, n is a positive odd integer not greater than 5, R is an aryl group selected from the class consisting of the benzene and naphthalene series, and R is a substituent selected from the group consisting ofhydrogen and acyl groups.

6. A polycyclic diketopyrimidine characterized by the following formula: V

r o=on-Nconi H 00cm 0 "I. A polycyclic diketopyrimidine characterized by the following formula:

=CHCH=CHNOaH 0 0 CH: ll 8. A polycyclic diketopyrimidine characterized by the following formula:

9. A method of producing a compound having the following formula: o

which comprises reacting a compound of the following formula:

with a compound of the following formula:

R 'NH-(M) n=N-R and its salts, wherein M represents a methenyl group, Z represents the non-metallic atoms necessary to complete a heterocyclic nucleus, 11. is a positive odd integer not greater than 5, R, R and R represent an aryl group selected from the class consisting of the benzene and naphthalene series and R is asubstituent selected from the group consisting of hydrogen and acyl groups.

10. A method as in claim 9 wherein n e als 1. 11. A method as in claim 9 wherein 1; equals 3. 12 A method as in claim 9 wherein n equals 5.

10 13. A method as in claim 9 wherein Z reprewith fl-anilinoacrolein anil hydrochloride in the sents the non-metallic atoms necessary to compresence of acetic anhydride. plete a thiazole nucleus.

16. A process which comprises reacting: 14. A process which comprises reacting 5 H 0 2 (i=0 mc 2 0:0 H:CN CH, H:-N 6H:

if 10 I? 0 o with diphenylformamidine in the presence of acetic anhydride. with glutaconic aldehyde dlanihde hydrochloride 15. A process which comprises reacting n the p n f lc a y n ALFRED W. ANISH. H; -N (3H1 

